EP0680928A1 - Process for the continuous preparation of nitrosyl chloride - Google Patents
Process for the continuous preparation of nitrosyl chloride Download PDFInfo
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- EP0680928A1 EP0680928A1 EP95105826A EP95105826A EP0680928A1 EP 0680928 A1 EP0680928 A1 EP 0680928A1 EP 95105826 A EP95105826 A EP 95105826A EP 95105826 A EP95105826 A EP 95105826A EP 0680928 A1 EP0680928 A1 EP 0680928A1
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- chloride
- nitrosyl chloride
- nitrosyl
- nitrogen dioxide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/16—Halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B21/00—Nitrogen; Compounds thereof
- C01B21/082—Compounds containing nitrogen and non-metals and optionally metals
- C01B21/083—Compounds containing nitrogen and non-metals and optionally metals containing one or more halogen atoms
- C01B21/084—Compounds containing nitrogen and non-metals and optionally metals containing one or more halogen atoms containing also one or more oxygen atoms, e.g. nitrosyl halides
- C01B21/0842—Halides of nitrogen oxides
- C01B21/0846—Nitrosyl chloride
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
Definitions
- the invention relates to a continuous process for the production of chlorine-free nitrosyl chloride from gaseous nitrogen dioxide and gaseous hydrogen chloride.
- nitrogen dioxide in the sense of the invention includes the nitrous oxide tetroxide which is in equilibrium therewith.
- Nitrosyl chloride is a frequently used NO ⁇ source in organic chemistry, for example for oximation, nitrosation and diazotization. Numerous processes have been described for the preparation of nitrosyl chloride.
- nitrosyl chloride is the preparation of aqua regia, although chlorine is also formed: 3 HCl + HNO3 ⁇ NOCl + Cl2 + H2O Introducing hydrogen chloride into a solution of nitrosylsulfuric acid in sulfuric acid leads to the formation of nitrosyl chloride according to the equation NOHSO4 + HCl ⁇ NOCl + H2SO4 As the reaction progresses, the method leads to less and less conversion, so that nitrosyl chloride / hydrogen chloride mixtures are formed with a continuously falling proportion of nitrosyl chloride. The disposal of the sulfuric acid containing chloride and nitrogen oxide as by-products is technically complex.
- nitrosyl chloride from alkyl nitrites in a low-salt medium is used, for example, in diazotization: RONO + HCl ⁇ NOCl + ROH C6H5 - NH2 + NOCl ⁇ C6H5 -N2 ⁇ Cl ⁇
- the alcohol that is formed can lead to undesired by-products via a Sandmeyer reaction.
- alkyl nitrites are mostly made from sodium nitrite, sulfuric acid and alcohol; this method is not particularly suitable for production on an industrial scale due to the high salt accumulation.
- nitrosyl chloride processes for the production of nitrosyl chloride are based on technically readily available nitrogen dioxide.
- nitrogen dioxide is passed into moistened alkali or alkaline earth chloride and obtained however, as a by-product, large amounts of alkali or alkaline earth nitrate.
- J. Chem. Phys. 18 (1950), 1411 a mixture of nitrosyl chloride, nitroxyl chloride and nitrogen dioxide is formed.
- nitrosyl chloride is prepared by converting liquid nitrogen dioxide and gaseous hydrogen chloride into nitric acid and must then be isolated discontinuously.
- the objects of the invention consisted in the provision of a continuously executable process, starting from technically well available nitrogen dioxide, for the production of nitrosyl chloride in good yield and in a purity which allows the nitrosyl chloride formed to undergo chlorination of amino heterocycles via the diazotization without further purification step , e.g. Aminopyridines and -pyrazoles to be used while avoiding by-products which are difficult to separate and difficult to dispose of, such as chlorine, nitrogen oxides and, in particular, large amounts of salt, the resulting nitric acid being obtained in a quality which is sufficient for further uses while avoiding additional cleaning measures.
- the invention thus relates to a process for the preparation of nitrosyl chloride from hydrogen chloride and nitrogen dioxide in a molar ratio of 0.4 to 1, preferably 0.4 to 0.8, in particular 0.5 to 0.7, at temperatures from 0 to 100, preferably 0 to 60 ° C, after which the reactants are passed in cocurrent from bottom to top through a reactor and the nitrosyl chloride formed at the top and the nitric acid formed at the bottom of the reactor.
- the reactants can be used as such or in a mixture with inert gases.
- inert gases include, for example, nitrogen, carbon dioxide, argon and the other noble gases.
- Such an inert gas can be fed into the reactor separately or premixed with one or both reactants.
- the volume ratio of inert gas / nitrogen dioxide can be, for example, 0 to 15, preferably 0.1 to 8.
- the use of water is not necessary for the process according to the invention; however, small amounts can be advantageous for diluting the nitric acid obtained.
- Excess hydrogen chloride can be removed after condensation of the nitrosyl chloride, optionally together with the inert gas, and returned to the reaction.
- the process according to the invention can in principle be carried out both under normal pressure and under reduced or increased pressure.
- the pressure range is from 0.5 to 10, preferably 0.7 to 7, particularly preferably 1 to 5 bar.
- Reactors to be used for the process according to the invention and the reaction conditions are chosen so that a residence time sufficient for complete reaction is ensured.
- Suitable reactors include, for example, reaction columns which ensure a large phase interface (gaseous / liquid) and intimate mixing of the liquid and the gaseous phase.
- trays such as bubble-cap trays, perforated perforated trays, valve trays, slotted trays, etc.
- trays such as bubble-cap trays, perforated perforated trays, valve trays, slotted trays, etc.
- Such columns with internals, fillings or packings and the fillings and packings themselves are commercially available and known to the person skilled in the art.
- Preferred reactors are tubular and have a length / diameter ratio of 10 to 150, preferably 20 to 70.
- Particularly preferred reactors are packed columns, as are used for fractional distillation, in a non-horizontal, ie in a vertical or oblique arrangement .
- the optimal size of the required phase interface in the reactor also depends on the temperature and the amount of gas. In general, however, surface / volume ratios of 1 to 20, preferably 5 to 15 cm -1 lead to satisfactory results.
- the invention furthermore relates to the use of the nitrosyl chloride prepared according to the invention in the chlorination of aminoheterocycles such as aminopyridines and pyrazoles via the diazotization.
- a glass column with a length of 80 cm and an inner diameter of 2 cm was filled with glass balls with a diameter of 3 mm.
- the reactants were introduced at the lower end.
- the top of the column was cooled with dry ice; there the condensed nitrosyl chloride was removed.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Die Erfindung betrifft ein kontinuierliches Verfahren zur Herstellung von chlorfreiem Nitrosylchlorid aus gasförmigem Stickstoffdioxid und gasförmigem Chlorwasserstoff. Der Begriff "Stockstoffdioxid" im Sinne der Erfindung schließt das damit im Gleichgewicht stehende Distickstofftetroxid ein.The invention relates to a continuous process for the production of chlorine-free nitrosyl chloride from gaseous nitrogen dioxide and gaseous hydrogen chloride. The term “nitrogen dioxide” in the sense of the invention includes the nitrous oxide tetroxide which is in equilibrium therewith.
Nitrosylchlorid ist in der organischen Chemie eine häufig verwandte NO⊕-Quelle, beispielsweise für Oximierungen, Nitrosierungen und Diazotierungen. Für die Herstellung von Nitrosylchlorid sind zahlreiche Verfahren beschrieben worden.Nitrosyl chloride is a frequently used NO ⊕ source in organic chemistry, for example for oximation, nitrosation and diazotization. Numerous processes have been described for the preparation of nitrosyl chloride.
Die bekannteste Herstellungsmethode für Nitrosylchlorid ist die Zubereitung von Königswasser, wobei allerdings auch Chlor entsteht:
3 HCl + HNO₃ → NOCl + Cl₂ + H₂O
Einleiten von Chlorwasserstoff in eine Lösung von Nitrosylschwefelsäure in Schwefelsäure führt zur Bildung von Nitrosylchlorid nach der Gleichung
NOHSO₄ + HCl → NOCl + H₂SO₄
Die Methode führt bei fortschreitender Reaktion zu immer geringerer Umsetzung, so daß Nitrosylchlorid/Chlorwasserstoff-Gemische mit einem ständig fallenden Nitrosylchlorid-Anteil entstehen. Die Entsorgung der als Nebenprodukte anfallenden Chlorid- und Stickoxid-haltigen Schwefelsäure ist technisch aufwendig.The best-known production method for nitrosyl chloride is the preparation of aqua regia, although chlorine is also formed:
3 HCl + HNO₃ → NOCl + Cl₂ + H₂O
Introducing hydrogen chloride into a solution of nitrosylsulfuric acid in sulfuric acid leads to the formation of nitrosyl chloride according to the equation
NOHSO₄ + HCl → NOCl + H₂SO₄
As the reaction progresses, the method leads to less and less conversion, so that nitrosyl chloride / hydrogen chloride mixtures are formed with a continuously falling proportion of nitrosyl chloride. The disposal of the sulfuric acid containing chloride and nitrogen oxide as by-products is technically complex.
Einige andere Verfahren gehen von Stickstoffmonoxid aus: Gemäß DE-AS 1 169 903 wird die Umsetzung mit Chlor in Gegenwart eines Katalysators entsprechend der Gleichung
empfohlen. Nach US-PS 2 366 518 verläuft die Umsetzung mit gasförmigem Chlorwasserstoff in Gegenwart von Sauerstoff über Distickstofftrioxid:
2 NO + 1/2 O₂ → N₂O₃
N₂O₃ + 2 HCl → 2 NOCl + H₂O.
Some other processes are based on nitrogen monoxide: According to DE-AS 1 169 903, the reaction with chlorine in the presence of a catalyst is in accordance with the equation
recommended. According to US Pat. No. 2,366,518, the reaction with gaseous hydrogen chloride in the presence of oxygen proceeds via dinitrogen trioxide:
2 NO + 1/2 O₂ → N₂O₃
N₂O₃ + 2 HCl → 2 NOCl + H₂O.
Zu wasserfreiem Nitrosylchlorid kommt man laut Comptes Rend. 204 (1932), 697 bis 699 durch Umsetzung von Distickstofftrioxid mit Thionylchlorid:
N₂O₃ + SOCl₂ → 2 NOCl + SO₂
Die genannten Verfahren sind mit dem Nachteil verbunden, daß sie das technisch schlecht verfügbare Stickstoffmonoxid als Ausgangsprodukt benötigen.According to Comptes Rend, you get anhydrous nitrosyl chloride. 204 (1932), 697 to 699 by reacting nitrous oxide with thionyl chloride:
N₂O₃ + SOCl₂ → 2 NOCl + SO₂
The processes mentioned have the disadvantage that they require the technically poorly available nitrogen monoxide as the starting product.
Die Bildung von Nitrosylchlorid aus Alkylnitriten in salzarmem Medium macht man sich beispielsweise bei der Diazotierung zunutze:
RONO + HCl ⇄ NOCl + ROH
C₆H₅ - NH₂ + NOCl → C₆H₅ -N₂⊕ Cl⊖
Allerdings kann der mitentstandene Alkohol über eine Sandmeyer-Reaktion zu unerwünschten Nebenprodukten führen. Darüber hinaus werden Alkylnitrite meistens aus Natriumnitrit, Schwefelsäure und Alkohol hergestellt; für eine Herstellung in technischem Maßstab ist diese Methode wegen des hohen Salzanfalls, also nicht besonders gut geeignet.The formation of nitrosyl chloride from alkyl nitrites in a low-salt medium is used, for example, in diazotization:
RONO + HCl ⇄ NOCl + ROH
C₆H₅ - NH₂ + NOCl → C₆H₅ -N₂ ⊕ Cl ⊖
However, the alcohol that is formed can lead to undesired by-products via a Sandmeyer reaction. In addition, alkyl nitrites are mostly made from sodium nitrite, sulfuric acid and alcohol; this method is not particularly suitable for production on an industrial scale due to the high salt accumulation.
Andere Verfahren zur Herstellung von Nitrosylchlorid gehen von technisch gut verfügbarem Stickstoffdioxid aus. Gemäß GB-PS 786 740 und FR-PS 1 333 767 leitet man Stickstoffdioxid in angefeuchtetes Alkali- oder Erdalkalichlorid und erhält allerdings als Nebenprodukt große Mengen Alkali- bzw. Erdalkalinitrat. Nach J. Chem. Phys. 18 (1950), 1411 entsteht dabei ein Gemisch aus Nitrosylchlorid, Nitroxylchlorid und Stickstoffdioxid.Other processes for the production of nitrosyl chloride are based on technically readily available nitrogen dioxide. According to GB-PS 786 740 and FR-PS 1 333 767, nitrogen dioxide is passed into moistened alkali or alkaline earth chloride and obtained however, as a by-product, large amounts of alkali or alkaline earth nitrate. According to J. Chem. Phys. 18 (1950), 1411, a mixture of nitrosyl chloride, nitroxyl chloride and nitrogen dioxide is formed.
Bei der Umsetzung von Stickstoffdioxid mit gasförmigem Chlorwasserstoff entsteht nach J. Amer. Chem. Soc. 63 (1942), 2520 als Nebenprodukt Chlor nach der Gleichung:
NO₂ + 2 HCl → NOCl + H₂O + 1/2 Cl₂
Laut US-PS 2 366 518 entsteht dabei wegen Nebenproduktbildung (Nitroxylchlorid, Salpetersäure, Stickoxide) nur wenig Nitrosylchlorid.When nitrogen dioxide is reacted with gaseous hydrogen chloride, according to J. Amer. Chem. Soc. 63 (1942), 2520 as a by-product chlorine according to the equation:
NO₂ + 2 HCl → NOCl + H₂O + 1/2 Cl₂
According to US Pat. No. 2,366,518, only a little nitrosyl chloride is formed due to by-product formation (nitroxyl chloride, nitric acid, nitrogen oxides).
Gemäß DE-OS 2 019 216 wird Nitrosylchlorid durch Umsetzung von flüssigem Stickstoffdioxid und gasförmigem Chlorwasserstoff in Salpetersäure hergestellt und muß anschließend diskontinuierlich isoliert werden.According to DE-OS 2 019 216, nitrosyl chloride is prepared by converting liquid nitrogen dioxide and gaseous hydrogen chloride into nitric acid and must then be isolated discontinuously.
Die Aufgaben der Erfindung bestand in der Bereitstellung eines kontinuierlich ausführbaren Verfahrens, ausgehend von technich gut verfügbarem Stickstoffdioxid, zur Herstellung von Nitrosylchlorid in guter Ausbeute und in einer Reinheit, die es erlaubt, das entstandene Nitrosylchlorid ohne weiteren Reinigungsschritt zur über die Diazotierung laufenden Chlorierung von Aminoheterocyclen, z.B. Aminopyridinen und -pyrazolen, einzusetzen unter Vermeidung von schwer abtrennbaren und schwierig zu entsorgenden Nebenprodukten, wie Chlor, Stickoxiden und insbesondere großen Salzmengen, wobei die anfallende Salpetersäure unter Vermeidung zusätzlicher Reinigungsmaßnahmen in einer für weitere Verwendungen ausreichenden Qualität anfallen soll.The objects of the invention consisted in the provision of a continuously executable process, starting from technically well available nitrogen dioxide, for the production of nitrosyl chloride in good yield and in a purity which allows the nitrosyl chloride formed to undergo chlorination of amino heterocycles via the diazotization without further purification step , e.g. Aminopyridines and -pyrazoles to be used while avoiding by-products which are difficult to separate and difficult to dispose of, such as chlorine, nitrogen oxides and, in particular, large amounts of salt, the resulting nitric acid being obtained in a quality which is sufficient for further uses while avoiding additional cleaning measures.
Es wurde nun überrraschenderweise gefunden, daß bei geeigneter Anordnung Stickstoffdioxid und Chlorwasserstoff in der Gasphase nahezu quantitativ zu Nitrosylchlorid hoher Reinheit umgesetzt werden können.It has now surprisingly been found that, with a suitable arrangement, nitrogen dioxide and hydrogen chloride in the gas phase can be converted almost quantitatively to high-purity nitrosyl chloride.
Gegenstand der Erfindung ist also ein Verfahren zur Herstellung von Nitrosylchlorid aus Chlorwasserstoff und Stickstoffdioxid im molaren Verhältnis von 0.4 bis 1, vorzugsweise 0.4 bis 0,8, insbesondere 0.5 bis 0,7, bei Temperaturen von 0 bis 100, vorzugsweise 0 bis 60°C, wonach man die Reaktanden im Gleichstrom von unten nach oben durch einen Reaktor führt und das gebildete Nitrosylchlorid oben und die gebildete Salpetersäure unten am Reaktor entnimmt.The invention thus relates to a process for the preparation of nitrosyl chloride from hydrogen chloride and nitrogen dioxide in a molar ratio of 0.4 to 1, preferably 0.4 to 0.8, in particular 0.5 to 0.7, at temperatures from 0 to 100, preferably 0 to 60 ° C, after which the reactants are passed in cocurrent from bottom to top through a reactor and the nitrosyl chloride formed at the top and the nitric acid formed at the bottom of the reactor.
Die Reaktanden können als solche oder in Mischung mit Inertgasen eingesetzt werden. Solche Inertgase umfassen beispielsweise Stickstoff, Kohlendioxid, Argon und die anderen Edelgase. Ein solches Inertgas kann getrennt oder mit einem oder beiden Reaktanden vorgemischt in den Reaktor eingespeist werden. Das Volumenverhältnis Inertgas/Stickstoffdioxid kann beispielsweise 0 bis 15, vorzugsweise 0.1 bis 8 betragen. Die Mitverwendung von Wasser ist für das erfindungsgemäße Verfahren nicht notwendig; geringe Mengen können jedoch zur Verdünnung der anfallenden Salpetersäure vorteilhaft sein.The reactants can be used as such or in a mixture with inert gases. Such inert gases include, for example, nitrogen, carbon dioxide, argon and the other noble gases. Such an inert gas can be fed into the reactor separately or premixed with one or both reactants. The volume ratio of inert gas / nitrogen dioxide can be, for example, 0 to 15, preferably 0.1 to 8. The use of water is not necessary for the process according to the invention; however, small amounts can be advantageous for diluting the nitric acid obtained.
Überschüssiger Chlorwasserstoff kann nach Kondensation des Nitrosylchlorids, gegebenenfalls zusammen mit dem Inertgas, entfernt und in die Reaktion zurückgeführt werden.Excess hydrogen chloride can be removed after condensation of the nitrosyl chloride, optionally together with the inert gas, and returned to the reaction.
Das erfindungsgemäße Verfahren läßt sich grundsätzlich sowohl bei Normaldruck als auch bei vermindertem oder erhöhtem Druck durchführen. Als Druckbereich kommt der von 0,5 bis 10, bevorzugt 0,7 bis 7, besonders bevorzugt 1 bis 5 bar in Frage.The process according to the invention can in principle be carried out both under normal pressure and under reduced or increased pressure. The pressure range is from 0.5 to 10, preferably 0.7 to 7, particularly preferably 1 to 5 bar.
Für das erfindungsgemäße Verfahren zu verwendende Reaktoren und die Reaktionsbedingungen werden so gewählt, daß eine für eine vollständige Umsetzung ausreichende Verweilzeit gewährleistet wird.Reactors to be used for the process according to the invention and the reaction conditions are chosen so that a residence time sufficient for complete reaction is ensured.
Geeignete Reaktoren umfassen beispielsweise Reaktionskolonnen, die eine große Phasengrenzfläche (gasförmig/flüssig) und eine innige Vermischung der flüssigen und der gasförmigen Phase gewährleisten. Dies kann durch den Einbau von Böden, wie Glockenböden, Sieblochböden, Ventilböden, Schlitzböden usw., wie sie für eine thermische Trennung üblich sind, durch Füllkörper aller Art, wie sie bei thermischen Trennoperationen üblich sind, oder durch die Ausrüstung der Kolonnen mit ungeordneten Füllkörpern aller Art oder mit geordneten Packungen aus Metall, Keramik, Kunststoff, Glas oder weiteren Materialien, die gegenüber den Reaktionspartnern des erfindungsgemäßen Verfahrens inert sind, erreicht werden. Solche Kolonnen mit Einbauten, Füllungen oder Packungen sowie die Füllungen und Packungen selbst sind handelsüblich und dem Fachmann bekannt.Suitable reactors include, for example, reaction columns which ensure a large phase interface (gaseous / liquid) and intimate mixing of the liquid and the gaseous phase. This can be done by installing trays, such as bubble-cap trays, perforated perforated trays, valve trays, slotted trays, etc., as are common for thermal separation, by packing of all kinds, as is customary in thermal separation operations, or by equipping the columns with unordered packing of all kinds or with ordered packings of metal, ceramic, plastic, glass or other materials which are inert towards the reactants of the process according to the invention become. Such columns with internals, fillings or packings and the fillings and packings themselves are commercially available and known to the person skilled in the art.
Bevorzugte Reaktoren sind röhrenförmig gebaut und besitzen ein Länge/Durchmesser-Verhältnis von 10 bis 150, vorzugsweise von 20 bis 70. Besonders bevorzugte Reaktoren sind Füllkörperkolonnen, wie sie für fraktionierte Destillationen eingesetzt werden, in nicht-waagrechter, also in senkrechter oder auch schräger Anordnung.Preferred reactors are tubular and have a length / diameter ratio of 10 to 150, preferably 20 to 70. Particularly preferred reactors are packed columns, as are used for fractional distillation, in a non-horizontal, ie in a vertical or oblique arrangement .
Die optimale Größe der nötigen Phasengrenzfläche im Reaktor hängt auch von Temperatur und Gasmenge ab. Im allgemeinen führen aber Oberflächen/Volumen-Verhältnisse von 1 bis 20, vorzugsweise 5 bis 15 cm⁻¹ zu zufriedenstellenden Ergebnissen.The optimal size of the required phase interface in the reactor also depends on the temperature and the amount of gas. In general, however, surface / volume ratios of 1 to 20, preferably 5 to 15 cm -1 lead to satisfactory results.
Die Belastung der Reaktoren, bezogen auf die gesamte eingespeiste Gasmenge (Stickstoffdioxid, Chlorwasserstoff und gegebenenfalls Inertgas), beträgt in der Regel 10 bis 3 000, bevorzugt 20 bis 2 000 und besonders bevorzugt 40 bis 1 000 Nl/l freien Volumens in der Reaktionskolonne pro Stunde (Nl = Liter unter Normalbedingungen).The loading of the reactors, based on the total amount of gas fed in (nitrogen dioxide, hydrogen chloride and possibly inert gas), is generally 10 to 3,000, preferably 20 to 2,000 and particularly preferably 40 to 1,000 Nl / l of free volume in the reaction column per Hour (Nl = liter under normal conditions).
Weiterer Gegenstand der Erfindung ist die Verwendung des erfindungsgemäß hergestellten Nitrosylchlorids bei über die Diazotierung laufenden Chlorierungen von Aminoheterocyclen wie Aminopyridinen und -pyrazolen.The invention furthermore relates to the use of the nitrosyl chloride prepared according to the invention in the chlorination of aminoheterocycles such as aminopyridines and pyrazoles via the diazotization.
Die Gasverhältnisse der nachfolgenden Beispiele beziehen sich auf das Volumen; Prozentangaben beziehen sich auf das Gewicht.The gas ratios in the examples below relate to the volume; Percentages refer to the weight.
Eine Glaskolonne mit einer Länge von 80 cm und einem inneren Durchmesser von 2 cm wurde mit Glaskugeln eines Durchmessers von 3 mm gefüllt. Am unteren Ende wurden die Reaktanden eingeführt. Der Kopf der Kolonne wurde mit Trockeneis gekühlt; dort wurde das kondensierte Nitrosylchlorid abgenommen.A glass column with a length of 80 cm and an inner diameter of 2 cm was filled with glass balls with a diameter of 3 mm. The reactants were introduced at the lower end. The top of the column was cooled with dry ice; there the condensed nitrosyl chloride was removed.
In das untere Ende der auf 25°C temperierten Kolonne wurden 15 l/h eines Chlorwasserstoff/Stickstoff-Gemisches (15:85) und nach 10 Minuten 1 l/h Stickstoffdioxid einer Temperatur von 25°C eingeleitet.15 l / h of a hydrogen chloride / nitrogen mixture (15:85) and, after 10 minutes, 1 l / h of nitrogen dioxide at a temperature of 25 ° C. were introduced into the lower end of the column, which was heated to 25 ° C.
25 ml DMF wurden in einem 500 ml-Kolben mit Chlorwasserstoff gesättigt. Nach Verdünnung mit 200 ml DMF und Abkühlen auf -10°C wurden 20 ml des hergestellten rohen NOCl zugesetzt. Bei 0°C tropfte man eine Lösung von 17,3 g 2-Amino-5-aminomethylpyridin in 100 ml DMF zu. Nach Aufwärmen auf Raumtemperatur und 1 h Nachrühren engte man am Rotationsverdampfer ein. Das Rohprodukt wurde mit 0,2 n Natronlauge neutralisiert und mit Dichlormethan extrahiert. Nach Trocknen mit wasserfreiem Natriumsulfat und Einengen am Rotationsverdampfer wurden 14,2 g Produkt erhalten, welches laut GC mit internem Standard 85,8 % an 2-Chlor-5-chlormethyl-pyridin (61,4 % d. Theorie) enthielt.25 ml of DMF was saturated with hydrogen chloride in a 500 ml flask. After dilution with 200 ml of DMF and cooling to -10 ° C., 20 ml of the crude NOCl prepared were added. A solution of 17.3 g of 2-amino-5-aminomethylpyridine in 100 ml of DMF was added dropwise at 0.degree. After warming up to room temperature and stirring for 1 h, the mixture was concentrated on a rotary evaporator. The crude product was neutralized with 0.2N sodium hydroxide solution and extracted with dichloromethane. After drying with anhydrous sodium sulfate and concentration on a rotary evaporator, 14.2 g of product were obtained which, according to GC with internal standard, contained 85.8% of 2-chloro-5-chloromethyl-pyridine (61.4% of theory).
Durch die Glaskolonne wurden 1 Stunde lang 20 l/h eines Chlorwasserstoff/Stickstoff-Gemischs (15:85) in eine Lösung von 2,6 g 94,5 %igen 2-Amiono-5-aminomethylpyridins in 70 ml DMF eingeleitet. Nach Abkühlung des Ansatzes auf 0°C wurden 1 Stunde 2 l/h Stickstoffdioxid zusätzlich in die Kolonne eingespeist. Nach üblicher Aufarbeitung wurde 2-Chlor-5-chlormethylpyridin in 72,4 % der Theorie erhalten. Als Nebenprodukt wurden 2,2 % 2-Chlor-5-hydroxymethylpyridin und 0,4 % 2,6-Dichlor-5-chlor-methylpyridin identifiziert. In der wässrigen Phase waren etwa 20 % der Theorie an 5-Chlormethylpyridon-2 vorhanden, welches auf bekannte Weise ebenfalls in 2-Chlor-5-chlormethylpyridin überführbar ist.20 l / h of a hydrogen chloride / nitrogen mixture (15:85) were passed through the glass column for 1 hour into a solution of 2.6 g of 94.5% 2-amino-5-aminomethylpyridine in 70 ml of DMF. After the mixture had cooled to 0 ° C., 2 l / h of nitrogen dioxide were additionally fed into the column for 1 hour. After the usual work-up, 2-chloro-5-chloromethylpyridine was obtained in 72.4% of theory. As a by-product, 2.2% 2-chloro-5-hydroxymethylpyridine and 0.4% 2,6-dichloro-5-chloromethylpyridine were identified. About 20% of theory of 5-chloromethylpyridone-2 was present in the aqueous phase, which can likewise be converted into 2-chloro-5-chloromethylpyridine in a known manner.
Durch die Glaskolonne wurden 1 Stunde lang 8 l/h eines Chlorwasserstoff/Stickstoff-Gemisches (15:85) in eine auf 0°C temperierte Lösung von 8,5 g 1-Methyl-5-aminopyrazolcarbonsäureethylester in 100 ml Chloroform geleitet. Dann schaltete man 1 Stunde lang 8 l/h Stickstoffdioxid zu. Die Reaktionsmischung wurde im Vakuum eingeengt, in 100 ml konzentrieerter Salzsäure gelöst und anschließend eine Lösung von 31 g Kupfersulfat und 28 g Kochsalz in 100 ml Wasser zugetropft. Nach 1,5 Stunden Rühren bei 50°C extrahierte man mit Chloroform, trocknete die vereinigten Extrakte mit wasserfreiem Natriumsulfat und engte am Rotationsverdampfer ein. 1-Methyl-5-chlorpyrazol-4carbonsäureethylester wurde in 76,7 % der Theorie erhalten.8 l / h of a hydrogen chloride / nitrogen mixture (15:85) were passed through the glass column for 1 hour into a solution of 8.5 g of 1-methyl-5-aminopyrazolecarboxylic acid ethyl ester in 100 ml of chloroform at 0 ° C. Then 8 l / h of nitrogen dioxide were added for 1 hour. The reaction mixture was concentrated in vacuo, dissolved in 100 ml of concentrated hydrochloric acid and then a solution of 31 g of copper sulfate and 28 g of common salt in 100 ml of water was added dropwise. After stirring at 50 ° C. for 1.5 hours, the mixture was extracted with chloroform, the combined extracts were dried with anhydrous sodium sulfate and concentrated on a rotary evaporator. 1-Methyl-5-chloropyrazole-4-carboxylic acid ethyl ester was obtained in 76.7% of theory.
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4415337 | 1994-05-02 | ||
| DE4415337A DE4415337A1 (en) | 1994-05-02 | 1994-05-02 | Process for the continuous production of nitrosyl chloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0680928A1 true EP0680928A1 (en) | 1995-11-08 |
Family
ID=6517012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP95105826A Withdrawn EP0680928A1 (en) | 1994-05-02 | 1995-04-19 | Process for the continuous preparation of nitrosyl chloride |
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| Country | Link |
|---|---|
| US (1) | US5552130A (en) |
| EP (1) | EP0680928A1 (en) |
| JP (1) | JPH07300304A (en) |
| DE (1) | DE4415337A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115382482A (en) * | 2022-10-28 | 2022-11-25 | 天津凯莱英医药科技发展有限公司 | System and method for continuously preparing 2-hydroxypyridine-N-oxide |
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| EP0650738B1 (en) * | 1993-10-28 | 2003-05-02 | Medrad, Inc. | Multi-patient fluid dispensing |
| CN102512186B (en) | 2004-11-16 | 2015-07-15 | 拜耳医疗保健公司 | Modeling of pharmaceutical propagation and response of patients to medication injection |
| EP2392379A3 (en) | 2004-11-24 | 2012-03-21 | Medrad, Inc. | Devices, systems and methods for fluid delivery |
| HUE040477T2 (en) | 2006-12-29 | 2019-03-28 | Bayer Healthcare Llc | Patient-based parameter generation systems for medical injection procedures |
| CN101742967B (en) | 2007-07-17 | 2014-06-11 | 梅德拉股份有限公司 | Devices, systems and methods for determination of parameters for a procedure, for estimation of cardiopulmonary function and for fluid delivery |
| US9421330B2 (en) | 2008-11-03 | 2016-08-23 | Bayer Healthcare Llc | Mitigation of contrast-induced nephropathy |
| KR20180015279A (en) | 2010-06-24 | 2018-02-12 | 바이엘 헬쓰케어 엘엘씨 | Modeling of pharmaceutical propagation and parameter generation for injection protocols |
| EP2758096A4 (en) | 2011-09-21 | 2015-07-01 | Bayer Medical Care Inc | Continuous multi-fluid delivery system and method |
| EP3489667B1 (en) | 2012-05-14 | 2021-05-05 | Bayer Healthcare LLC | Systems and methods for determination of pharmaceutical fluid injection protocols based on x-ray tube voltage |
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| EP3423130A1 (en) | 2016-03-03 | 2019-01-09 | Bayer Healthcare LLC | System and method for improved fluid delivery in multi-fluid injector systems |
| WO2019046260A1 (en) | 2017-08-31 | 2019-03-07 | Bayer Healthcare Llc | Method for dynamic pressure control in a fluid injector system |
| WO2019046261A1 (en) | 2017-08-31 | 2019-03-07 | Bayer Healthcare Llc | System and method for drive member position and fluid injector system mechanical calibration |
| US11141535B2 (en) | 2017-08-31 | 2021-10-12 | Bayer Healthcare Llc | Fluid path impedance assessment for improving fluid delivery performance |
| CA3067625C (en) | 2017-08-31 | 2024-04-30 | Bayer Healthcare Llc | Injector pressure calibration system and method |
| US11478581B2 (en) | 2017-08-31 | 2022-10-25 | Bayer Healthcare Llc | Fluid injector system volume compensation system and method |
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| US2366518A (en) * | 1941-12-26 | 1945-01-02 | Dow Chemical Co | Manufacture and use of nitrosyl chloride |
| US3214240A (en) * | 1962-12-13 | 1965-10-26 | Halby Chemical Co Inc | Process of reacting chlorides with nitric acid |
| DE2019216A1 (en) * | 1969-04-21 | 1970-10-22 | Ici Ltd | Process for the production of nitrosyl chloride |
| US4557920A (en) * | 1983-10-17 | 1985-12-10 | Versar Inc. | Process for making fuming nitric acid |
| WO1990009958A1 (en) * | 1989-02-27 | 1990-09-07 | Mallinckrodt, Inc. | Preparation of nitrosyl fluoride |
| EP0508215A1 (en) * | 1991-04-06 | 1992-10-14 | Bayer Ag | Process for the preparation of 2-chloro-pyridines |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB786740A (en) * | 1954-06-23 | 1957-11-27 | Fisons Ltd | Production of potassium nitrate |
| NL287101A (en) * | 1961-12-22 | |||
| FR1333767A (en) * | 1962-04-28 | 1963-08-02 | Pierrefitte Soc Gen D Engrais | Simultaneous manufacturing process of nitrosyl chloride and alkali or alkaline earth nitrate |
| DE1169903B (en) * | 1962-08-16 | 1964-05-14 | Basf Ag | Process for the production of nitrosyl chloride |
| US3481704A (en) * | 1966-06-27 | 1969-12-02 | Shell Oil Co | Process for the preparation of nitrosyl chloride |
| US4026674A (en) * | 1975-10-30 | 1977-05-31 | Commonwealth Oil Refining Co., Inc. | Multi-stage reactor |
-
1994
- 1994-05-02 DE DE4415337A patent/DE4415337A1/en not_active Withdrawn
-
1995
- 1995-04-19 EP EP95105826A patent/EP0680928A1/en not_active Withdrawn
- 1995-04-25 US US08/429,277 patent/US5552130A/en not_active Expired - Fee Related
- 1995-04-27 JP JP7127341A patent/JPH07300304A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2366518A (en) * | 1941-12-26 | 1945-01-02 | Dow Chemical Co | Manufacture and use of nitrosyl chloride |
| US3214240A (en) * | 1962-12-13 | 1965-10-26 | Halby Chemical Co Inc | Process of reacting chlorides with nitric acid |
| DE2019216A1 (en) * | 1969-04-21 | 1970-10-22 | Ici Ltd | Process for the production of nitrosyl chloride |
| US4557920A (en) * | 1983-10-17 | 1985-12-10 | Versar Inc. | Process for making fuming nitric acid |
| WO1990009958A1 (en) * | 1989-02-27 | 1990-09-07 | Mallinckrodt, Inc. | Preparation of nitrosyl fluoride |
| EP0508215A1 (en) * | 1991-04-06 | 1992-10-14 | Bayer Ag | Process for the preparation of 2-chloro-pyridines |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115382482A (en) * | 2022-10-28 | 2022-11-25 | 天津凯莱英医药科技发展有限公司 | System and method for continuously preparing 2-hydroxypyridine-N-oxide |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07300304A (en) | 1995-11-14 |
| US5552130A (en) | 1996-09-03 |
| DE4415337A1 (en) | 1995-11-09 |
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